Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

PAX6

Reviewed July 2014

What is the official name of the PAX6 gene?

The official name of this gene is “paired box 6.”

PAX6 is the gene's official symbol. The PAX6 gene is also known by other names, listed below.

What is the normal function of the PAX6 gene?

The PAX6 gene belongs to a family of genes that play a critical role in the formation of tissues and organs during embryonic development. The members of the PAX gene family are also important for maintaining the normal function of certain cells after birth. To carry out these roles, the PAX genes provide instructions for making proteins that attach to specific areas of DNA and help control the activity (expression) of particular genes. On the basis of this action, PAX proteins are called transcription factors.

During embryonic development, the PAX6 protein is thought to turn on (activate) genes involved in the formation of the eyes, the brain and spinal cord (central nervous system), and the pancreas. Within the brain, the PAX6 protein is involved in the development of a specialized group of brain cells that process smell (the olfactory bulb). Additionally, researchers believe that the PAX6 protein controls many aspects of eye development before birth. After birth, the PAX6 protein likely regulates the expression of various genes in many structures of the eyes.

Does the PAX6 gene share characteristics with other genes?

The PAX6 gene belongs to a family of genes called homeobox (homeoboxes). It also belongs to a family of genes called PAX (paired boxes).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the PAX6 gene related to health conditions?

aniridia - caused by mutations in the PAX6 gene

More than 280 mutations in the PAX6 gene have been found to cause aniridia, which is an absence of the colored part of the eye (the iris). Most of these mutations create a premature stop signal in the instructions for making the PAX6 protein and lead to the production of an abnormally short, nonfunctional protein. As a result, there is less PAX6 protein to regulate the activity of other genes.

The majority of mutations that cause aniridia occur within the PAX6 gene; however, some disease-causing mutations occur in neighboring regions of DNA that normally regulate the expression of the PAX6 gene, known as regulatory regions. Mutations in PAX6 gene regulatory regions reduce the expression of the PAX6 gene. These mutations lead to a shortage of functional PAX6 protein, which disrupts the formation of the eyes during development.

Gillespie syndrome - caused by mutations in the PAX6 gene

At least two mutations in the PAX6 gene have been identified in people with Gillespie syndrome, a disorder characterized by eye abnormalities including absence of part of the iris (partial aniridia), difficulty coordinating movements (ataxia), and mild to moderate intellectual disability. The mutations that cause Gillespie syndrome result in the absence of the PAX6 protein or production of a nonfunctional PAX6 protein that is unable to bind to DNA and regulate the activity of other genes. This lack of functional protein disrupts embryonic development, especially the development of the eyes and brain, leading to the signs and symptoms of Gillespie syndrome.

Peters anomaly - caused by mutations in the PAX6 gene

At least two mutations in the PAX6 gene have been found to cause Peters anomaly. This condition is characterized by the abnormal development of certain structures at the front of the eye and clouding of the clear front surface of the eye (cornea). The mutations that cause Peters anomaly change single protein building blocks (amino acids) in the PAX6 protein. These mutations reduce but do not eliminate the protein's function and are less severe than mutations that cause aniridia (described above). The mutations that cause Peters anomaly reduce the PAX6 protein's ability to bind to DNA, disrupting its role as a transcription factor. As a result, normal development of the eye is impaired, leading to the features of Peters anomaly. The PAX6 gene mutations that cause Peters anomaly can cause other related eye disorders in members of the same family.

Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome - associated with the PAX6 gene

The PAX6 gene is located in a region of chromosome 11 that is deleted in people with Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome, more commonly known by the acronym WAGR syndrome. As a result of this deletion, affected individuals are missing one copy of the PAX6 gene in each cell. A loss of the PAX6 gene is associated with the characteristic eye features of WAGR syndrome, including aniridia, and may affect brain development.

other disorders - caused by mutations in the PAX6 gene

Mutations in the PAX6 gene can cause eye problems other than aniridia and Peters anomaly. The mutations that cause these eye problems occur in one copy of the PAX6 gene in each cell. Most of these mutations change single amino acids in the PAX6 protein. These mutations reduce but do not eliminate the protein's normal function, impairing its role as a transcription factor.

Individuals with these relatively mild PAX6 gene mutations may be born with pupils that are not centrally positioned in the eye (ectopia papillae), small eyes (microphthalmia), and underdeveloped optic nerves, structures that carry information from the eyes to the brain. Mild PAX6 mutations can also result in a gap or split in structures that make up the eye (coloboma) or an underdeveloped region at the back of the eye responsible for sharp central vision (the fovea). Additional conditions caused by these PAX6 gene mutations may be present at birth or develop later. These conditions may include a clouding of the lens of the eye (cataracts), involuntary eye movements (nystagmus), and inflammation of the front surface of the eye called the cornea (keratitis).

It is unclear why the effects of some mutations in the PAX6 gene are limited to the eye, while other mutations affect the development of many parts of the body.

Where is the PAX6 gene located?

Cytogenetic Location: 11p13

Molecular Location on chromosome 11: base pairs 31,784,791 to 31,817,960

The PAX6 gene is located on the short (p) arm of chromosome 11 at position 13.

The PAX6 gene is located on the short (p) arm of chromosome 11 at position 13.

More precisely, the PAX6 gene is located from base pair 31,784,791 to base pair 31,817,960 on chromosome 11.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about PAX6?

You and your healthcare professional may find the following resources about PAX6 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the PAX6 gene or gene products?

  • AN
  • AN2
  • D11S812E
  • MGC17209
  • MGDA
  • paired box gene 6
  • paired box gene 6 isoform a
  • paired box gene 6 isoform b
  • PAX6_HUMAN

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding PAX6?

acids ; ataxia ; cell ; central nervous system ; chromosome ; cornea ; deletion ; disability ; DNA ; embryonic ; fovea ; gene ; inflammation ; involuntary ; keratitis ; mental retardation ; nervous system ; nystagmus ; olfactory bulb ; pancreas ; protein ; regulatory regions ; syndrome ; transcription ; transcription factor ; tumor ; Wilms tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References

  • Azuma N, Yamaguchi Y, Handa H, Tadokoro K, Asaka A, Kawase E, Yamada M. Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations. Am J Hum Genet. 2003 Jun;72(6):1565-70. Epub 2003 Apr 29. (http://www.ncbi.nlm.nih.gov/pubmed/12721955?dopt=Abstract)
  • Chao LY, Huff V, Strong LC, Saunders GF. Mutation in the PAX6 gene in twenty patients with aniridia. Hum Mutat. 2000;15(4):332-9. (http://www.ncbi.nlm.nih.gov/pubmed/10737978?dopt=Abstract)
  • Graziano C, D'Elia AV, Mazzanti L, Moscano F, Guidelli Guidi S, Scarano E, Turchetti D, Franzoni E, Romeo G, Damante G, Seri M. A de novo nonsense mutation of PAX6 gene in a patient with aniridia, ataxia, and mental retardation. Am J Med Genet A. 2007 Aug 1;143A(15):1802-5. (http://www.ncbi.nlm.nih.gov/pubmed/17595013?dopt=Abstract)
  • Hanson IM. PAX6 and congenital eye malformations. Pediatr Res. 2003 Dec;54(6):791-6. Epub 2003 Oct 15. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14561779?dopt=Abstract)
  • Hingorani M, Williamson KA, Moore AT, van Heyningen V. Detailed ophthalmologic evaluation of 43 individuals with PAX6 mutations. Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2581-90. doi: 10.1167/iovs.08-2827. Epub 2009 Feb 14. (http://www.ncbi.nlm.nih.gov/pubmed/19218613?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5080)
  • OMIM: PAIRED BOX GENE 6 (http://omim.org/entry/607108)
  • Robinson DO, Howarth RJ, Williamson KA, van Heyningen V, Beal SJ, Crolla JA. Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia. Am J Med Genet A. 2008 Mar 1;146A(5):558-69. doi: 10.1002/ajmg.a.32209. (http://www.ncbi.nlm.nih.gov/pubmed/18241071?dopt=Abstract)
  • Ticho BH, Hilchie-Schmidt C, Egel RT, Traboulsi EI, Howarth RJ, Robinson D. Ocular findings in Gillespie-like syndrome: association with a new PAX6 mutation. Ophthalmic Genet. 2006 Dec;27(4):145-9. (http://www.ncbi.nlm.nih.gov/pubmed/17148041?dopt=Abstract)
  • Tzoulaki I, White IM, Hanson IM. PAX6 mutations: genotype-phenotype correlations. BMC Genet. 2005 May 26;6:27. (http://www.ncbi.nlm.nih.gov/pubmed/15918896?dopt=Abstract)
  • van Heyningen V, Williamson KA. PAX6 in sensory development. Hum Mol Genet. 2002 May 15;11(10):1161-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12015275?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: July 2014
Published: September 1, 2015